Targeting brain circuits for addiction, relapse

Could a once-a-month alcoholism shot keep some of the highest-risk heroin addicts from relapse? A drug that wakes up narcoleptics treat cocaine addiction? An old antidepressant fight methamphetamine?

This is the next frontier in substance abuse: Better understanding of how addiction overlaps with other brain diseases is sparking a hunt to see if a treatment for one might also help another.

We're not talking about attempts just to temporarily block an addict's high. Today's goal is to change the underlying brain circuitry that leaves substance abusers prone to relapse.

It's "a different way of looking at mental illnesses, including substance abuse disorders," says National Institute on Drug Abuse Director Dr. Nora Volkow, who on Monday urged researchers at the American Psychiatric Association's annual meeting to get more creative in the quest for brain-changing therapies for addiction.

Rather than a problem in a single brain region, scientists increasingly believe that psychiatric diseases are a result of dysfunctioning circuits spread over multiple regions, leaving them unable to properly communicate and work together. That disrupts, for example, the balance between impulsivity and self-control that plays a crucial role in addiction.

These networks of circuits overlap, explaining why so many mental disorders share common symptoms, such as mood problems. It's also a reason that addictions - to nicotine, alcohol or various types of legal or illegal drugs - often go hand-in-hand with post-traumatic stress disorder, depression, schizophrenia and other mental illnesses.

Think of it as if the brain were an orchestra, its circuits the violins and the piano and the brass section, all smoothly starting and stopping their parts on cue, Volkow told The Associated Press.

"That orchestration is disrupted in psychiatric illness," she explains. "There's not a psychiatric disease that owns one particular circuit."

So NIDA, part of the National Institutes of Health, is calling for more research into treatments that could target circuits involved with cognitive control, better decision-making and resistance to impulses. Under way:

-Manufacturer Alkermes Inc. recently asked the Food and Drug Administration to approve its once-a-month naltrexone shot - already sold to treat alcoholism - to help people kick addiction to heroin and related drugs known as opioids. Scientists have long known that naltrexone pills can block heroin's effects, but the pills last only a day so skipping a dose lets addicts get high again. Alkermes' studies show the monthly version, named Vivitrol, can help reduce heroin use long-term.

But Volkow points to a study in Russia that found naltrexone shots also reduced cravings for the illegal drug. That's important, she says, because the treatment may be extinguishing too-active reward circuitry in the brain that conditioned people to keep using, and thus may prevent relapse.

With NIDA funding, Dr. Charles O'Brien of the University of Pennsylvania is studying that question in a tough-to-treat population, prison parolees. They quickly relapse as they return home and so-called "cue-induced cravings" reawaken, strong desires triggered by seeing friends they once did drugs with or simply passing by their old seller's street corner. At five sites around the Northeast, O'Brien's study will test if six months of Vivitrol can stop that cycle.

-Studies at several hospitals around the country suggest modafinil, used to fend off the sudden sleep attacks of narcolepsy, also can help cocaine users abstain. It may act as a mild stimulant that reduces their desire for the drug. But back to those brain circuits, cocaine causes damage in networks involved in reasoning, weighing decisions and overcoming impulses. Some research suggests modafinil counters that problem by improving what scientists call executive function, higher-order decision-making that involves those capabilities.

-An old antidepressant, bupropion, that's already used for smoking cessation now is being tested for methamphetamine addiction, based on early-stage research suggesting it somehow blunts the high. But Volkow says addiction makes the brain more sensitive to stressors that in turn trigger negative mood circuitry, so she wants antidepressants also to be tested in combination with other addiction medications.

Medication isn't the only option. Biofeedback teaches people with high blood pressure to control their heart rate. O'Brien's colleagues at Penn are preparing to test if putting addicts into MRI machines for real-time brain scans could do something similar, teaching them how to control their impulses to take drugs.

"It's controlling your own brain," O'Brien says. While the idea is extremely early-stage, "we think that it's very promising."